Through the use of osmotic stress, it has been found that some 60 water molecules bind to hemoglobin when it switches from the "tense" deoxy to the "relaxed" oxy forms. It appears that this water should be treated as a liganding species much as oxygen or other allosteric effectors. The alpha-toxin trans-membrane channel from Staphylococcus aureus has been reconstituted into bilayer membranes and osmotically stressed to provide the information that 600 water molecules enter and leave this channel when it opens and closes under applied voltage. This channel appears also to have different pH sensitivity from each side of the membrane. Swelling of secretory granules after release from beige mouse mast cells appears to be governed by hydration/dehydration events that can be described by thermodynamic analysis similar to that developed to analyze macromolecular assembly in vitro. The coupling of swelling concomitant to secretion with the exchange of counterions to the polysaccharide matrix suggests a further parallel between in vivo and in vitro processes.